MYC regulates metabolism through vesicular transfer of glycolytic kinases

Amplification of the proto-oncogene MYCN is a key molecular aberration in high-risk neuroblastoma and predictive of poor outcome in this childhood malignancy. We investigated the role of MYCN in regulating the protein cargo of extracellular vesicles (EVs) secreted by tumour cells that can be internalized by recipient cells with functional consequences. Using a switchable MYCN system coupled to mass spectrometry analysis, we found that MYCN regulates distinct sets of proteins in the EVs secreted by neuroblastoma cells. EVs produced by MYCN-expressing cells or isolated from neuroblastoma patients induced the Warburg effect, proliferation and c-MYC expression in target cells. Mechanistically, we linked the cancer-promoting activity of EVs to the glycolytic kinase pyruvate kinase M2 (PKM2) that was enriched in EVs secreted by MYC-expressing neuroblastoma cells. Importantly, the glycolytic enzymes PKM2 and hexokinase II were detected in the EVs circulating in the bloodstream of neuroblastoma patients, but not in those of non-cancer children. We conclude that MYC-activated cancers might spread oncogenic signals to remote body locations through EVs.

Oral cavity tumors in children. Diagnostic approach

Although the majority of lesions reported in children and adolescents are benign, it should be recognized that oral malignant tumors do occur in children. The incidence of childhood malignancy is greatest in the 1st year of life, with the second peak to be found at 2–3 years of age. Many clinicians do believe that oral cancer is particularly aggressive in young patients, and is associated with poorer survival compared to adults. Numerous early reports of oral cancer in young adults concluded that the disease was more aggressive, and prognosis was poorer than in older adults. Purpose of this study is to make a literature review on the diagnostic methods of the tumors of oral cavity in children. Conclusion. Despite the progress in technology and medicine paraclinical examination methods in determining tumors of the oral cavity in children haven’t been developed and studied enough, thourder studies have to be done in order to create diagnostic protocols for the pediatric population.

Rare Childhood Malignancy

This small collection of six original research papers and two review articles in the Special Issue “Rare Childhood Malignancy” highlights the diversity and importance of empirical research into childhood malignancy, a theme that underpins the significant advances that have been made in treating the diseases that constitute cancers in children [...]

Rare Presentation of Acute Lymphoblastic Leukemia – A Case Report

Acute lymphoblastic leukaemia / lymphoblastic lymphoma is the most common childhood malignancy. Leukaemia and lymphoma are clinical presentations of the same disease. It is estimated that approximately 2500 to 3500 new cases are diagnosed each year in the United States, with an incidence of approximately 3.4 cases per 100,000. Number of the cases vary all over the world which is due to diagnostic and reporting differences.1,2 Leukaemia, especially acute types, can lead to intracranial haemorrhage (ICH) with high morbidity and mortality. It was reported that ICH occurred in 2.8 % adult patients with haematological malignancies. 3,4 But majority of cases presented with intraparenchymal haemorrhage, only rare cases have been seen to present with sub dural haemorrhage.

Pattern and Outcome of Childhood Cancer in Rivers State University Teaching Hospital

Introduction: Childhood cancer is on the increase globally with a heterogenous distribution in the type seen in different localities, age groups, and gender. So also, is the outcome of treatment variable in different countries and is dependent on the availability of funds, drugs, medical equipment among others. Aim: To determine the pattern and outcome of childhood cancer in Rivers State University Teaching Hospital (RSUTH). Methods: A 5-year retrospective study was carried out in RSUTH from January 2015 to December 2019. The case notes of all children aged 1-16years with diagnosis of childhood malignancy were retrieved and only those with histopathologic diagnosis of cancer and complete data were included in the study. Results: Thirty-two children aged 1-16years, with a median age of 6years, 24 (75%) males and 8 (25%) females were recruited for the study. The median duration of symptoms was 3 months. Majority of the care givers (75%) were of low socio-economic class. Leukaemia 8 (25%) and lymphomas 5 (18.8%) were the common malignancies seen and 50% had metastatic disease at presentation. Fever (62.5%), weight loss (56.3%) and pallor (46.9%) were common complaints given, while chemotherapy alone 5 (15.6%) or in combination with surgery 5 (15.6%) was the most given treatment. Three (9.4%) children completed treatment and are alive, 28.1% requested for discharge against medical advice and 28.1% died. Conclusion: Leukemia and lymphomas are common forms of childhood malignancy in our facility. Majority of the caregivers were poor and unable to complete the required treatment of their children.

Acute Myeloid Leukemia Presenting as a Cardiac Mass

Leukemias are the most common childhood malignancy. It is a systemic disease presenting with different signs and symptoms. Extramedullary manifestations, in particular myeloid sarcoma (MS), are extremely rare, often challenging to identify, even more challenging to diagnose, and more than often misdiagnosed owing to its similarity with other solid tumors. We describe a previously healthy boy, aged 4 years, who had a cardiac mass lesion, presumed to be a MS, noted in the right atrium at the time of initial routine echocardiography. The lesion resolved without surgical intervention following the institution of multi-agent chemotherapy.

A History of Large for Gestational Age at Birth and Future Risk for Pediatric Neoplasms: A Population-Based Cohort Study

Objective: The aim of this study was to evaluate the association between large for gestational age (LGA) at birth and future risk of childhood neoplasm. Study design: a population-based cohort to compare the long-term risk (up to the age of 18 years) of childhood neoplasms (benign and malignant) in children that were born LGA vs. those that were appropriate for gestational age (AGA), between the years 1991–2014. Childhood neoplasms diagnosis were defined according to international classification of disease 9 (ICD-9) codes recorded medical files. Kaplan–Meier survival curves were used in order to compare cumulative incidence of oncological morbidity over the study period. The Cox proportional hazards model was used to control for confounders. Results: 231,344 infants met the inclusion criteria; out of those 10,369 were diagnosed LGA at birth. Children that were LGA at birth had a higher incidence of leukemia (OR 2.25, 95%CI 1.08–4.65, p = 0.025) as well as kidney tumors (OR = 4.7, 95%CI = 1.02–21.9, p = 0.028). In addition, cumulative incidence over time of childhood malignancies, leukemia, and kidney tumors were significantly higher in LGA children (Log Rank = 0.010, 0.021, and 0.028, respectively). In a Cox regression model controlling for other perinatal confounders, LGA at birth remained independently associated with an increased risk for childhood malignancy (adjusted HR 1.51, 95%CI 1.02–2.23, p = 0.039). Conclusion: LGA at birth is associated with increased long-term risk for childhood malignancy and specifically leukemia and kidney tumors. This possible link may help to improve current knowledge regarding potential exposures that are associated with childhood cancer development.